The objective of this work is to separate the manifold activities of the prostaglandins at diverse target sites by judicious alteration of their structure utilizing synthetic procedures worked out in this laboratory. A second objective is to gain further information by nmr techniques on the conformation of prostaglandins in solution and to study the effects on conformation when binding occurs to a specific target macromolecule, namely, the placental prostaglandin 15- dehydrogenase of human origin, a vital soluble enzyme catalyzing the first step in the metabolic inactivation of the prostaglandins. Specifically the project consists of the following components: 1) Completion of a 7-step synthesis of the prostaglandins (probably the shortest on record), 2) Synthesis of (16R) and (16S)-16- fluoroprostaglandins and their 13-dehydro derivatives and diastereomers, 3) Synthesis of 10, 10-difluoroprostaglandins, 4) Biosynthesis of 1,3,5,7,9,11,13,15,17,19-deca-C13-PGF2 alpha and 5) Relaxation measurements on the above isotopically labelled prostaglandins per se and of the enzyme substrate complex to ascertain regions of specific binding between enzyme and substrate.